PROJECT SUMMARY ? OVERALL Worldwide, cervical cancer is the fourth leading cause of cancer incidence and mortality; 80% of cervical cancers arise and 87% of cervical cancer deaths occur in low and lower-middle income countries. In Peru, cervical cancer is diagnosed at a rate of 17 per 100,000 women per year, and in the DR at 23 per 100,000 annually among women in the general population. The burden of cervical cancer is substantially increased among women living with HIV (WLWH), although the exact rates are not well described. Although HPV vaccines are safe and effective as primary prevention, they have limited availability in low resource settings and the optimal regimen of vaccine doses for HIV-infected persons in such settings has not been defined. Furthermore, delivery of cervical cancer prevention and treatment of precursors for WLWH in low- and middle- income countries is impeded by approaches that are often costly, require multiple visits and extensive provider training. Moreover, many of these are not suitable for delivery within an HIV primary care model. The Cervical Cancer Prevention Partnership (C2P2) Center involves two clinical trial sites, in Peru and the Dominican Republic, and three cores (Administrative and Coordinating Core, Statistics and Data Management Core and Central Laboratory Core) in Seattle. Investigators in the C2P2 Center will jointly design, conduct and analyze three clinical trials with the goal of moving toward elimination of cervical cancer among highly vulnerable populations with HIV in low resource settings in Latin America and the Caribbean (LAC). We seek to improve the quality and efficiency of prevention strategies using new approaches that will augment the existing infrastructure at local HIV clinics in Peru and the Dominican Republic (DR). The aims of the proposed Clinical Trials Center span the continuum of cervical cancer prevention from vaccination through treatment. The trials we propose will address these technical issues and provide a more direct pipeline for prevention. In this C2P2 Center, our overarching aims are: ? Specific Aim 1: To test the effectiveness of novel approaches to cervical cancer prevention in high- burden HIV-infected populations in Peru and the DR by performing three clinical trials. One will assess the ability of HPV vaccination regimens to elicit long-lasting B cell responses, and two will assess novel screening, triage, and treatment approaches that will improve the quality and reach of prevention in low-resource settings throughout the LAC region. ? Specific Aim 2: To build a robust multidirectional collaboration between study investigators at all sites that serves the needs of providers who care for women living with HIV. The Center will engage with leaders in the region to enhance the sustainability of efforts that target future elimination of cervical cancer through multiple high-impact prevention and treatment strategies.